Drug Reduces Prostate Cancer Diagnosis in Men at Increased Risk

April 28, 2009 – A drug widely used to shrink enlarged prostates has been shown to lower the risk of prostate cancer by 23 percent in men who have an increased risk of the disease, according to results of an international clinical trial presented April 27 at the American Urological Association annual meeting in Chicago.

The four-year, phase III trial known as REDUCE is the first to look at chemoprevention for prostate cancer in men at increased risk for the disease. The trial involved 8,200 men ages 50 to 75 who were randomly assigned to receive a placebo or a daily 0.5 milligram dose of dutasteride (Avodart), manufactured by GlaxoSmithKline.

"Dutasteride has the potential to offer many thousands of men a way to reduce their risk of being diagnosed with prostate cancer," says the study's lead investigator, Gerald Andriole, MD, a urologist at the Siteman Cancer Center and chief of urologic surgery at Washington University School of Medicine. "This should ultimately mean more men will avoid treatment for prostate cancer and the cost and unwanted side effects associated with treatment."

Men in the study had elevated PSA levels (2.5 to 10 ng/ml), indicating they were at increased risk of prostate cancer. They also had undergone biopsies that found no evidence of cancer within six months prior to enrolling in the trial. Therefore, these men either did not have prostate cancer or possibly had microscopic tumors that were too small to be detected by the prestudy biopsy.

The investigators performed scheduled biopsies on the men two years after they enrolled in the study and again after four years. After two years, prostate cancer was found in 17.2 percent of the men who took a placebo, compared with 13.4 percent who took dutasteride. After four years, prostate cancer was diagnosed in another 11.8 percent of men who received a placebo and 9.1 percent who received dutasteride.

"In these men, the most likely explanation is that dutasteride worked by shrinking tumors or slowing their growth, thereby making them less likely to be detected by a biopsy," Andriole says.

The reduction in prostate cancer risk was constant across multiple subgroups of men in REDUCE. Dutasteride worked well in men regardless of age, prostate size, PSA level and a family history of prostate cancer.

Dutasteride was approved by the U.S. Food and Drug Administration in 2001 for the treatment of benign prostatic hyperplasia (BPH). This condition causes frequent urination that is difficult or painful. The current study was conducted because data collected as part of the FDA approval process suggested that men with BPH who took dutasteride had fewer diagnoses of prostate cancer.

The investigators found no significant increase in aggressive tumors among men who took dutasteride. This outcome was closely watched because an earlier trial of a similar BPH drug for the prevention of prostate cancer – finasteride (Proscar) – found that while the drug lowered cancer risk, it was linked to more aggressive tumors, although a later analysis of the data suggested that may not be the case.

Over the course of the current study, 6.8 percent of men in the placebo group and 6.7 percent of men in the dutasteride group were found to have aggressive, high-grade tumors, defined as a Gleason score of 7 to 10.

"We are very encouraged by this finding," Andriole says. "Clearly, the data show dutasteride did not lead to more high-grade tumors, even though they would have been easier to detect in the dutasteride-treated men due to their smaller prostates."

Andriole and his colleagues also noted that dutasteride improved the PSA test's ability to detect prostate cancer, particularly aggressive tumors.

Prostate cancer and BPH often go hand in hand; both conditions can raise PSA levels. Dutasteride works by blocking two forms of the enzyme 5-alpha reductase, which converts testosterone produced in the testicles into dihydrotestosterone. In contrast, finasteride only inhibits one form of the enzyme. Dihydrotestosterone is known to be a potent stimulator of benign prostate growth and the development of prostate cancer.

The REDUCE investigators also found that dutasteride significantly reduced episodes of urinary retention and the need for surgery to alleviate BPH in men taking the drug, compared to those taking a placebo.

The two most common side effects associated with dutasteride, the researchers noted, were low rates of erectile dysfunction and decreased libido, which are consistent with earlier studies of the drug.

Prostate cancer is the second most deadly cancer in men after lung cancer. Worldwide, it is responsible for more than 221,000 deaths annually.

The REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial was conducted at 250 sites in 42 countries around the world. The study was funded by GlaxoSmithKline. Andriole is chairman of the REDUCE steering committee and a consultant for the company.